Genome Sequencing of an Extended Series of NDM-Producing Klebsiella pneumoniae Isolates from Neonatal Infections in a Nepali Hospital Characterizes the Extent of Community- versus Hospital-Associated Transmission in an Endemic Setting

被引:105
作者
Stoesser, N. [1 ]
Giess, A. [1 ]
Batty, E. M. [2 ]
Sheppard, A. E. [1 ]
Walker, A. S. [3 ]
Wilson, D. J. [1 ,2 ]
Didelot, X. [4 ]
Bashir, A. [5 ]
Sebra, R. [5 ]
Kasarskis, A. [5 ]
Sthapit, B. [6 ]
Shakya, M. [6 ]
Kelly, D. [3 ,7 ]
Pollard, A. J. [3 ,7 ]
Peto, T. E. A. [1 ]
Crook, D. W. [1 ]
Donnelly, P. [2 ]
Thorson, S. [6 ]
Amatya, P. [6 ]
Joshi, S. [6 ]
机构
[1] Univ Oxford, Nuffield Dept Clin Med, Oxford, England
[2] Wellcome Trust Ctr Human Genet, Oxford, England
[3] Univ Oxford, Oxford Univ Hosp NHS Trust, NIHR Biomed Res Ctr, Oxford, England
[4] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England
[5] Icahn Sch Med Mt Sinai, New York, NY 10029 USA
[6] Patan Hosp, Dept Pediat, Kathmandu, Nepal
[7] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford Vaccine Grp, Oxford, England
基金
英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;
关键词
METALLO-BETA-LACTAMASE; ENTEROBACTERIACEAE; ALGORITHMS; RESISTANCE; ALIGNMENT; DIVERSE;
D O I
10.1128/AAC.03900-14
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
NDM-producing Klebsiella pneumoniae strains represent major clinical and infection control challenges, particularly in resource-limited settings with high rates of antimicrobial resistance. Determining whether transmission occurs at a gene, plasmid, or bacterial strain level and within hospital and/or the community has implications for monitoring and controlling spread. Whole-genome sequencing (WGS) is the highest-resolution typing method available for transmission epidemiology. We sequenced carbapenem-resistant K. pneumoniae isolates from 26 individuals involved in several infection case clusters in a Nepali neonatal unit and 68 other clinical Gram-negative isolates from a similar time frame, using Illumina and PacBio technologies. Within-outbreak chromosomal and closed-plasmid structures were generated and used as data set-specific references. Three temporally separated case clusters were caused by a single NDM K. pneumoniae strain with a conserved set of four plasmids, one being a 304,526-bp plasmid carrying blaNDM-1. The plasmids contained a large number of antimicrobial/heavy metal resistance and plasmid maintenance genes, which may have explained their persistence. No obvious environmental/human reservoir was found. There was no evidence of transmission of outbreak plasmids to other Gram-negative clinical isolates, although bla(NDM) variants were present in other isolates in different genetic contexts. WGS can effectively define complex antimicrobial resistance epidemiology. Wider sampling frames are required to contextualize outbreaks. Infection control may be effective in terminating outbreaks caused by particular strains, even in areas with widespread resistance, although this study could not demonstrate evidence supporting specific interventions. Larger, detailed studies are needed to characterize resistance genes, vectors, and host strains involved in disease, to enable effective intervention.
引用
收藏
页码:7347 / 7357
页数:11
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